The primary focus of this research project is to investigate the central neuoendocrine mechanisms involved in the initiatign and maintenance of high blood pressure. More specifically, we are concerned with the brain angiotensin/vasopressin axis - its chemical and immunochemical characterizaton, its relationship in the control of blood pressure and fluid/electrolyte balance, and finally its possible role in the pathogenesis of hypertension. Since angiotensin II (A-II) has been reported to be present within the central nervous system and is known to exert effects on blood pressure, vasopressin release and water/electrolyte balance, the possibility exists that A-II via its interaction with neurohypophyseal secretion may be important in the development of hypertension. This proposal is designed to first characterize these neuropeptides using a combination of high pressure liquid chromatography (HPLC for separation of small polypeptides), radioimmunoassay, and immunocytochemistry, and then to evaluate the changes which might occur in the spontaneously hypertensive rat (SHR). Further experiments are planned to investigate the interactions between A-II and vasopressin and their possible role in the etiology of spontaneous hypertension. Acute and chronic physiological experiments are designed to evaluate the effect of intraventricullr A-II or its antagonists on blood pressure, vasopressin secretion, and fluid/electrolyte balance in the conscious unrestrained rat.